In the present study, we investigated the apoptotic effects of isosclerone from marine-derived fungi on human breast cancer MCF-7 cells. Treatment with isosclerone exhibited a characteristic feature of apoptosis including significant cytotoxicity and DNA fragmentation in cancer cells. In addition, The apoptosis induction abilities of the isosclerone was studied by analyzing the expression of caspase-3, -8 and -9, Bcl-2 family, NF-κ-B P50, P65, and IKK proteins. Western blot and RT-PCR analysis have indicated that isosclerone induce cancer cells apoptosis through down-regulated Bcl-2 family and up-regulated caspases, and activating the NF-κ-B signaling pathway. Our data demonstrate that isosclerone specifically binds to crystal structure of apoptosis regulator BCL-2 and pseudo-activated procaspase-3 proteins through down-regulated Bcl-2 family and up-regulated caspases, and activating the NF-κ-B signaling pathway. Our proof-of-principle study should have a positive impact on future drug discovery.
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